Method for production of bis(hydroxy-aromatic)compounds

ABSTRACT

Disclosed is a method for preparing a bis(hydroxy-aromatic) compound which comprises the steps of: contacting at least one halo-substituted hydroxy-aromatic compound in a solvent mixture comprising water and at least one organic solvent in the presence of at least one base, at least one catalyst comprising palladium and hydrogen gas at a pressure in a range of between atmospheric pressure and 350 Kilopascals.

CROSS REFERENCE TO RELATED APPLICATION

This Application is related to the following U.S. Patent Application:U.S. Patent Application Ser. No. 10/680,776 entitled “PROCESS FOR THERECOVERY OF DIHYDROXYBIARYL COMPOUNDS” being filed concurrentlyherewith, which is hereby incorporated herein by reference in itsentirety.

BACKGROUND OF THE INVENTION

The present invention relates a method for producingbis(hydroxy-aromatic) compounds. More particularly, it relates a methodfor producing bis(hydroxy-aromatic) compounds in a catalytic reductivecoupling reaction using hydrogen as the reductant.

Bis (hydroxy-aromatic) compounds find many uses in chemicalapplications, such as in dyes, plastics, pharmaceuticals andagrochemicals. In particular applications bis(hydroxy-aromatic)compounds are common monomers for use in forming polymers, such aspolycarbonates, polyestercarbonates, polyesters, polyethers,polyetherimides, polyether ketones, polyetheretherketones and the like.Methods to produce bis(hydroxy-aromatic) compounds by reductive couplingof halo-substituted hydroxy-aromatic compounds are known in the art. Theuse of hydrogen as the stoichiometric reductant in such couplingreactions is also known. Busch et al. in Chemische Berichte, vol. 62,pp. 2612-2620 (1929) and in J. Prakt. Chem., vol. 146, pp. 1-55 (1936)describe a reductive coupling method for producing biaryl compounds fromhalo-substituted aromatic starting materials. The method uses highpressure hydrogen as reductant. However, halo-substituted aromaticstarting materials also bearing polar substituents give lowerselectivity to biaryl product. For example 4-bromophenol gives only 13%of 4,4′-dihydroxybiphenyl. Therefore, there is a continuing need formethods to synthesize bis(hydroxy-aromatic) compounds which provide highconversion of starting material and high selectivity tobis(hydroxy-aromatic) compound product.

BRIEF DESCRIPTION OF THE INVENTION

The present inventors have discovered a method to preparebis(hydroxy-aromatic) compounds by reductive coupling ofhalo-substituted hydroxy-aromatic compounds using hydrogen as areductant at low pressure. The use of low pressure hydrogen reductantprovides surprisingly high levels of both starting material conversionand also selectivity to the desired bis(hydroxy-aromatic) product. Theuse of low pressure also conserves hydrogen reactant and obviates theneed for expensive high pressure reaction equipment. The use of lowpressure hydrogen reductant also allows halo-substitutedhydroxy-aromatic compounds with less reactive chloro-substituents to beused as starting materials.

In one of its embodiments the present invention comprises a method forpreparing a bis(hydroxy-aromatic) compound which comprises the step of:contacting at least one halo-substituted hydroxy-aromatic compound in asolvent mixture comprising water and at least one organic solvent in thepresence of at least one base, at least one catalyst comprisingpalladium and hydrogen gas at a pressure in a range of betweenatmospheric pressure and 350 kilopascals

Various other features, aspects, and advantages of the present inventionwill become more apparent with reference to the following description,examples, and appended claims.

DETAILED DESCRIPTION OF THE INVENTION

In the following specification and the claims which follow, referencewill be made to a number of terms which shall be defined to have thefollowing meanings. The singular forms “a”, “an” and “the” includeplural referents unless the context clearly dictates otherwise.“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where the event occurs and instances where it does not.

Bis(hydroxy-aromatic) compounds of the present invention are produced bycatalytic reductive coupling of halo-substituted hydroxy-aromaticcompounds (sometimes referred to hereinafter as starting material). Saidbis(hydroxy-aromatic) compounds are attached together at the carbonatoms which formerly bore the reactive halo substituent on eachhydroxy-aromatic ring of the starting material. In an illustrativeexample 4-halophenol produces 4,4′-dihydroxybiphenyl. More particularly,in the present context a hydroxy-aromatic compound comprises anyaromatic moiety substituted on a ring carbon atom of at least onearomatic ring with a hydroxy substituent or a moiety convertible to ahydroxy substituent under the coupling reaction conditions. Suitablehalo-substituted hydroxy-aromatic compounds include, but are not limitedto, phenolic compounds with at least one halo substituent and optionallyat least one additional substituent. In particular embodiments the halosubstituents comprise iodo, bromo or chloro. In another particularembodiment the halo substituent is bromo. In yet another particularembodiment the halo substituent is chloro. The halo substituent is in aposition on the aromatic ring relative to the hydroxy substituent suchthat catalytic reductive coupling may proceed. In particular embodimentsthe halo substituent is on a carbon atom on the aromatic ring adjacentto the carbon atom bearing the hydroxy substituent or separated by atleast one or two carbon atoms from the carbon atom bearing the hydroxysubstituent. In other particular embodiments the halo substituent is ona carbon atom on the aromatic ring separated by at least two carbonatoms from the carbon atom bearing the hydroxy substituent. Optionaladditional substituents comprise those which do not interfere withcatalytic reductive coupling of halo-substituted hydroxy-aromaticcompounds. In particular embodiments optional additional substituentscomprise alkyl, aryl, ether, alkyl ether, aryl ether, carboxylic acid,carboxylic ester, an additional hydroxy substituent, and the like.Optional additional substituents may also comprise at least one otherhalo substituent, although in such instances it is sometimes preferredthat only one halo substituent be reactive toward catalytic reductivecoupling and any remaining halo substituents be less reactive either forsteric or electronic reasons. Mixtures comprising more than one optionaladditional substituent may be present on the halo-substitutedhydroxy-aromatic compound.

Bis(hydroxy-aromatic) compounds produced by the method of the presentinvention may be symmetrical or unsymmetrical. Symmetricalbis(hydroxy-aromatic) compounds may result from homo-coupling of twomoles of the same starting material. Symmetrical bis(hydroxy-aromatic)compounds may also result from coupling of one mole of adi-halo-substituted hydroxy-aromatic compound with two moles of amono-halo-substituted hydroxy-aromatic compound. Saiddi-halo-substituted hydroxy-aromatic compound comprises two reactivehalogen substituents. Unsymmetrical bis(hydroxy-aromatic) compounds mayresult from hetero-coupling of one mole of a first halo-substitutedhydroxy-aromatic compound with one mole of a second halo-substitutedhydroxy-aromatic compound. In embodiments wherein more than one productcould be formed, the desired product may selectively precipitate fromthe reaction mixture as it is formed.

The term “alkyl” as used in the various embodiments of the presentinvention is intended to designate both linear alkyl, branched alkyl,aralkyl, cycloalkyl, bicycloalkyl, tricycloalkyl and polycycloalkylradicals containing carbon and hydrogen atoms, and optionally containingatoms in addition to carbon and hydrogen, for example atoms selectedfrom Groups 15, 16 and 17 of the Periodic Table. The term “alkyl” alsoencompasses that alkyl portion of alkoxide groups. In variousembodiments normal and branched alkyl radicals are those containing from1 to about 32 carbon atoms, and include as illustrative non-limitingexamples C₁-C₃₂ alkyl optionally substituted with one or more groupsselected from C₁-C₃₂ alkyl, C₃-C₁₅ cycloalkyl or aryl; and C₃-C₁₅cycloalkyl optionally substituted with one or more groups selected fromC₁-C₃₂ alkyl. Some particular illustrative examples comprise methyl,ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tertiary-butyl, pentyl,neopentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. Someillustrative non-limiting examples of cycloalkyl and bicycloalkylradicals include cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl,cycloheptyl, bicycloheptyl and adamantyl. In various embodiments aralkylradicals are those containing from 7 to about 14 carbon atoms; theseinclude, but are not limited to, benzyl, phenylbutyl, phenylpropyl, andphenylethyl. In various embodiments aryl radicals used in the variousembodiments of the present invention are those substituted orunsubstituted aryl or heteroaryl radicals containing from 6 to 18 ringcarbon atoms. Some illustrative non-limiting examples of these arylradicals include C₆-C₁₅ aryl optionally substituted with one or moregroups selected from C₁-C₃₂ alkyl, C₃-C₁₅ cycloalkyl or aryl. Someparticular illustrative examples of aryl radicals comprise substitutedor unsubstituted phenyl, biphenyl, toluyl and naphthyl. Heteroarylgroups comprise those containing from about 3 to about 10 ring carbonatoms, and include, but are not limited to, triazinyl, pyrimidinyl,pyridinyl, furanyl, thiazolinyl and quinolinyl.

In some particular embodiments of the present invention suitablehalo-substituted hydroxy-aromatic compounds comprise halo-substitutedhydroxybenzene compounds with at least one additional alkyl substituent.In other particular embodiments of the present invention suitablehalo-substituted hydroxy-aromatic compounds comprise halo-substitutedhydroxybenzene compounds with no additional substituents. In still otherparticular embodiments suitable halo-substituted hydroxy-aromaticcompounds comprise bromo- or chloro-substituted phenols or naphthols. Inyet still another particular embodiment a suitable halo-substitutedhydroxy-aromatic compound includes, but is not limited to,2,6-dimethyl4-bromophenol, 4-bromo-1-naphthol, 4-chloro-1-naphthol,4-bromo-ortho-alkylphenol, 4-chloro-ortho-alkylphenol,4-bromo-ortho-cresol, 4-chloro-ortho-cresol, 4-bromophenol,4-chloro-phenol, and the like and mixtures thereof.

The reductive coupling reaction of the present invention is performed inthe presence of hydrogen gas as reductant. Although hydrogen gas ispreferred, the coupling reaction may be performed alternatively in thepresence of at least one reactant which generates hydrogen gas under thereaction conditions. Optionally, the hydrogen gas may be diluted withone or more inert gases such as, but not limited to, nitrogen or argon.When so diluted, the percentage of hydrogen gas present in the gasmixture is in a range of between about 40 mole % and about 99 mole %, orin a range of between about 50 mole % and about 98 mole %, or in a rangeof between about 60 mole % and about 98 mole %, or in a range of betweenabout 70 mole % and about 98 mole % based on total moles gas present.Hydrogen gas may be added in any convenient manner to the reactionmixture. In one embodiment a gas comprising hydrogen is sparged througha reaction mixture at some convenient rate. In a preferred embodiment areaction mixture is agitated under an atmosphere comprising hydrogengas. A surprising discovery of the present invention is that hydrogengas reductant is more effective at low pressure rather than at highpressure for both high conversion of starting material and highselectivity to desired bis(hydroxy-aromatic) product under the reactionconditions of the present invention. In particular embodiments, when thereaction is run under an atmosphere comprising hydrogen gas, thehydrogen gas is present at a pressure of less than about 350 kilopascals(kPa), or at a pressure of less than about 275 kilopascals (kPa), or ata pressure of less than about 200 kilopascals (kPa), or at a pressure ofless than about 150 kPa, or at a pressure of less than about 110 kPa. Inother particular embodiments the hydrogen gas is present at a pressurein a range of between about atmospheric pressure and about 200 kPa, orin a range of between about atmospheric pressure and about 150 kPa, orin a range of between atmospheric pressure and about 110 kPa. In thepresent context the concept of “pressure of hydrogen gas” refers to thepressure of pure hydrogen gas or to the partial pressure of hydrogen gasin a mixture with at least one other inert gas. Although the inventionis in no way limited by any theory of operation, it is believed that thehigh selectivity to desired bis(hydroxy-aromatic) product exhibited inthe present invention may be at least in part related to the decreasedtendency for starting material to be reduced to the correspondingdehalogenated hydroxy-aromatic compound under high pressure hydrogenreaction conditions of the prior art.

Catalysts suitable for performing the reductive coupling reactions arethose which comprise palladium. In particular embodiments of theinvention suitable catalysts comprise palladium metal or any palladiumcompound that forms palladium metal under the reaction conditions.Palladium metal when employed as a catalyst may optionally be supportedon an inert support, said support being insoluble in the reaction mediaIllustrative supports include, but are not limited to, carbon, alumina,barium carbonate, barium sulfate, calcium carbonate, strontiumcarbonate, silica and the like. The amount of palladium employed may bereadily determined without undue experimentation by those skilled in theart and is generally an amount sufficient to provide high conversion ofstarting material and high selectivity to desired bis(hydroxy-aromatic)product under the reaction conditions. In some embodiments the amount ofpalladium employed is in a range of between about 0.01 wt. % and about 5wt. %, or in a range of between about 0.05 wt. % and about 4 wt. %, orin a range of between about 0.1 wt. % and about 3 wt. %, or in a rangeof between about 0.5 wt. % and about 2 wt. % based on the weight of thehalo-substituted hydroxy-aromatic compound.

The reductive coupling reaction of the present invention is performed inthe presence of at least one base. In general the base may comprise anybase of sufficient strength to neutralize hydrogen halide formed duringthe reductive coupling reaction. Typically, alkaline earth hydroxides oralkali metal hydroxides may be employed. At least one of sodiumhydroxide or potassium hydroxide may be employed in some embodiments ofthe invention. Mixtures of bases are also suitable. In particularembodiments it has been surprisingly discovered that the use ofpotassium hydroxide results in significantly improved conversion ofstarting material and improved selectivity to desiredbis(hydroxy-aromatic) product under the reaction conditions of thepresent invention.

The amount of base employed is at least sufficient to neutralize all ofthe hydrogen halide formed. In other embodiments of the invention theamount of base employed is at least sufficient to neutralize all of theacidic species in the reaction mixture. In still other embodiments theamount of base present is at least one molar equivalent in relation tomoles of halo-substituted hydroxy-aromatic compound present. In otherembodiments of the invention the base may be present in stoichiometricexcess in relation to the amount of hydrogen halide that will be formed.In still other embodiments the amount of base present is at least 2molar equivalents in relation to moles of halo-substitutedhydroxy-aromatic compound present. In still other embodiments the amountof base present is less than four molar equivalents in relation to molesof halo-substituted hydroxy-aromatic compound present. In still otherembodiments the amount of base present is in a range of between about1.5 molar equivalents and about 4 molar equivalents, or in a range ofbetween about 1.8 molar equivalents and about 4 molar equivalents, or ina range of between about 2 molar equivalents and about 4 molarequivalents in relation to moles of halo-substituted hydroxy-aromaticcompound present.

A base may be added to the reaction mixture in any convenient manner. Insome embodiments the base is added in pure form or in a solutioncomprising water. When added in pure form, solid bases may optionally besubjected to a particle size reduction step to provide higher surfacearea solid. When added in a solution comprising water, the base may bepresent in said water solution at a concentration in a range of betweenabout 5 wt. % and about 95 wt. %, or at a concentration in a range ofbetween about 10 wt. % and about 80 wt. %, or at a concentration in arange of between about 20 wt. % and about 70 wt. %, or at aconcentration in a range of between about 40 wt. % and about 60 wt. %.In some embodiments at least a portion of base is present at thebeginning of the reaction and further base is added as the reactionproceeds or at a point where a desired level of conversion of startingmaterial has occurred. In a preferred embodiment all of the base ispresent at the beginning of the reaction.

The reductive coupling reaction of the present invention is performed ina solvent mixture comprising water and at least one organic solvent. Inparticular embodiments the solvent mixture is such that solubility ofstarting material is maximized. In other particular embodiments thesolvent mixture is such that solubility of base is maximized. In stillother particular embodiments the solvent mixture is such that solubilityof both starting material and base is maximized. The ratio of water toorganic solvent suitable to maximize solubility of any particularstarting material or base or mixture of starting material and base maybe easily determined by those skilled in the art without undueexperimentation. In various embodiments of the invention suitableorganic solvents comprise those which are substantially miscible withwater. In the present context substantially miscible means that underthe reaction conditions less than about 5 wt. % of said organic solventis immiscible with water based on the combined weight of water andorganic solvent. In some particular embodiments suitable organicsolvents comprise alkyl alcohols or alkyl glycols which aresubstantially water-soluble. In other particular embodiments suitableorganic solvents comprise methanol, ethanol, ethylene glycol and thelike. Mixtures of organic solvents may also be employed.

In some embodiments of the invention the amount of organic solvent thatmay be present is greater than 1 wt. % or greater than 15 wt. % orgreater than 20 wt. % or greater than 25 wt. % or greater than 30 wt. %or greater than 35 wt. % or greater than 40 wt. % or greater than 45 wt.% or greater than 50 wt. % based on the weight of organic solvent andwater. Within this range the amount of organic solvent that may bepresent is less than 80 wt. % or less than 70 wt. % or less than 60 wt.% based on the weight of organic solvent and water. In other embodimentsthe amount of organic solvent that may be present is in a range ofbetween about 5 wt. % and about 60 wt. %, or in a range of between about10 wt. % and about 55 wt. %, or in a range of between about 15 wt. % andabout 50 wt. %, or in a range of between about 20 wt. % and about 45 wt.%, or in a range of between about 25 wt. % and about 45 wt. %, based onthe weight of organic solvent and water.

In specific embodiments the concentration of starting material insolvent mixture is in a range of between about 5 wt. % and about 50 wt.%, or in a range of between about 10 wt. % and about 45 wt. %, or in arange of between about 15 wt. % and about 35 wt. %, or in a range ofbetween about 20 wt. % and about 30 wt. %, based on the weight of theentire reaction mixture. It will be understood that the startingmaterial and base may be initially at least partially insoluble in thesolvent mixture and will progressively dissolve in increasing amounts asthe reaction proceeds and starting material and base are removed fromsolution.

It is to be understood that the reductive coupling reaction mixture mayoptionally comprise any intermediates resulting from reaction of asingle reaction mixture component or of two or more components of thereaction mixture. In some particular embodiments the reductive couplingreaction mixture may optionally comprise any intermediates resultingfrom reaction of catalyst with at least one other reaction mixturecomponent.

Suitable reaction temperatures for performance of catalytic reductivecoupling are those temperatures which promote the coupling reaction at areasonable rate to form bis(hydroxy-aromatic) product, and may bereadily determined by those skilled in the art without undueexperimentation. In particular embodiments suitable reactiontemperatures are above about 45° C. In other particular embodimentssuitable reaction temperatures are in the range of about 45° C. to theboiling point of the solvent media under the pressure of the reactionconditions. In still other particular embodiments suitable reactiontemperatures are in the range of about 45° C. to about 100° C.; or in arange of about 55° C. to about 90° C.; or in a range of about 65° C toabout 85° C.

The reductive coupling reaction may be performed in batch, semi-batch orcontinuous mode. The duration of the reaction is such that a desiredlevel of bis(hydroxy-aromatic) product is formed. Suitable durations maybe readily determined by those skilled in the art without undueexperimentation. In some embodiments the duration of the reaction issuch that there is no more conversion of starting materials or no moreformation of the desired product or both. In some particularembodiments, depending upon such factors as the mass and stoichiometryof the reactants, the duration of the reaction is for about 60-120minutes.

The course of the reaction may be monitored using known methodsincluding, but not limited to, removal of an analytical sample andanalysis by at least one of high performance liquid chromatography(HPLC), gas chromatography (GC), nuclear magnetic resonance spectroscopy(NMR), infrared spectroscopy (IR), ultraviolet spectroscopy (UV), orlike methods. The course of the reaction may also be monitored in situwithout removal of an analytical sample.

Following conversion to a desired level of bis(hydroxy-aromatic)product, the reaction mixture may be worked up and thebis(hydroxy-aromatic) product isolated using known methods. In oneembodiment insoluble catalyst species may be removed from the reactionmixture by one or more steps of filtration, centrifugation, decantationor like methods. If desired, the catalyst may be reused, optionallyfollowing a reactivation step. Depending primarily upon the molar ratioof base to starting material, the bis(hydroxy-aromatic) compound productof the reaction may be initially formed wholly or at least partly as thebis(aromatic hydroxide) salt comprising the bis(hydroxy-aromatic)compound product and cation derived from the base. In another embodimentthe reaction mixture is quenched with an acid to convert anybis(aromatic hydroxide) salt to neutral, bis(hydroxy-aromatic) product.Following removal of solvent, the bis(hydroxy-aromatic) product mayoptionally be purified by known methods, including, but not limited to,at least one step of crystallization, distillation, sublimation, dryingor like methods. In other embodiments of the invention thebis(hydroxy-aromatic) product may be used in some subsequent processwithout isolation from solvent mixture.

The method of the invention provides surprisingly high levels of bothstarting material conversion and also selectivity to the desiredbis(hydroxy-aromatic) product. In particular embodiments conversion ofstarting material may be greater then 20 mole %, or greater than 25 mole%, or greater than 30 mole %, or greater than 35 mole %, or greater than40 mole %, or greater than 45 mole %, or greater than 50 mole %, orgreater than 55 mole %, or greater than 60 mole %. In other particularembodiments conversion of starting material may be in a range of betweenabout 20 mole % and about 90 mole %, or in a range of between about 25mole % and about 90 mole %, or in a range of between about 30 mole % andabout 90 mole %, or in a range of between about 35 mole % and about 90mole %, or in a range of between about 40 mole % and about 90 mole %, orin a range of between about 45 mole % and about 90 mole %, or in a rangeof between about 50 mole % and about 90 mole %, or in a range of betweenabout 55 mole % and about 90 mole %. In particular embodiments theselectivity to the desired bis(hydroxy-aromatic) product may be greaterthen 20 mole %, or greater than 25 mole %, or greater than 30 mole %, orgreater than 35 mole %, or greater than 40 mole %, or greater than 45mole %, or greater than 50 mole %, or greater than 55 mole %, or greaterthan 60 mole %. In other particular embodiments the selectivity to thedesired bis(hydroxy-aromatic) product may be in a range of between about20 mole % and about 90 mole %, or in a range of between about 25 mole %and about 90 mole %, or in a range of between about 30 mole % and about90 mole %, or in a range of between about 35 mole % and about 90 mole %,or in a range of between about 40 mole % and about 90 mole %, or in arange of between about 45 mole % and about 90 mole %, or in a range ofbetween about 50 mole % and about 90 mole %, or in a range of betweenabout 55 mole % and about 90 mole %.

Without further elaboration, it is believed that one skilled in the artcan, using the description herein, utilize the present invention to itsfullest extent. The following examples are included to provideadditional guidance to those skilled in the art in practicing theclaimed invention. The examples provided are merely representative ofthe work that contributes to the teaching of the present application.Accordingly, these examples are not intended to limit the invention, asdefined in the appended claims, in any manner.

EXAMPLES 1-22 AND COMPARATIVE EXAMPLES 1-2

General Experimental procedure: In a typical batch experiment, sixteen3-dram vials containing stir bars were charged with 1 mole percentpalladium based on moles 4-bromophenol starting material (added as 5%palladium on carbon), water, optionally an organic solvent and4-bromophenol as shown in Table 1. Then the vials were loaded into analuminum block which was suspended in a 1-gallon Parr autoclave reactor.After the reactor was sealed, the head space of the reactor wastypically flushed with hydrogen gas and then pressurized to a givenpressure with hydrogen gas. Comparative Examples (C.Ex.) 1 and 2 werepressurized to high pressure. The reactor was then heated to atemperature of 75° C., and stirred for 90 minutes. After the reactionwas complete, the reactor was typically cooled to room temperature anddepressurized. From each of the sixteen vials an aliquot of known masswas taken and worked up using standard procedures for BPLC analysis ofunreacted starting material, 4,4′-dihydroxybiphenyl, and phenol. Theanalytical results are shown in Table 1. The term “equivalents of base”refers to molar equivalents relative to 4-bromophenol. The values forwt. % solvent refer to weight percent relative to the weight of thewater/organic solvent combination.

TABLE 1 Experiment Equivalents Wt. % H₂ Pressure Wt. % % % Selectivityfor 4,4′- No. Base of base Solvent solvent (kPa) 4-bromophenolConversion dihydroxybiphenyl C. Ex. 1 NaOH 1 methanol 33 1723 33 55 5 C.Ex. 2 NaOH 2 methanol 33 1723 33 72 17 Ex. 1 NaOH 0.5 methanol 24 103 3317 36 Ex. 2 NaOH 1 methanol 33 103 33 45 47 Ex. 3 NaOH 2 methanol 41 10333 63 50 Ex. 4 KOH 0.5 methanol 21 103 30 6 30 Ex. 5 KOH 1 methanol 30103 30 19 65 Ex. 6 KOH 2 methanol 43 103 30 29 70 Ex. 7 NaOH 2iso-propanol 33 103 33 20 9 Ex. 8 NaOH 2 ethanol 33 103 33 12 3 Ex. 9NaOH 2 methanol 33 103 33 81 43 Ex. 10 NaOH 2 sulfolane 33 103 33 7 12Ex. 11 KOH 2 iso-propanol 30 103 30 9 21 Ex. 12 KOH 2 ethanol 30 103 303 11 Ex. 13 KOH 2 methanol 30 103 30 41 68 Ex. 14 KOH 2 sulfolane 30 10330 5 19 Ex. 15 NaOH 2 — 0 103 29 56 2 Ex. 16 NaOH 2 methanol 15 103 2928 40 Ex. 17 NaOH 2 methanol 28 103 29 17 54 Ex. 18 NaOH 2 methanol 42103 29 19 49 Ex. 19 KOH 2 — 0 103 29 29 12 Ex. 20 KOH 2 methanol 15 10329 40 63 Ex. 21 KOH 2 methanol 29 103 29 58 67 Ex. 22 KOH 2 methanol 37103 25 55 65

Comparative Experiments 1 and 2 show that reactions run under highpressure of hydrogen provide high conversion of 4-bromophenol startingmaterial but low selectivity to the desired 4,4′-dihydroxybiphenylproduct. In contrast Examples 2 and 3 of the invention run underconditions similar to those of Comparative Examples 1 and 2 but at lowhydrogen pressure provide high conversion of 4bromophenol startingmaterial and also surprisingly higher selectivity to the desired4,4′-dihydroxybiphenyl product compared to the Comparative Examples.Examples wherein potassium hydroxide was used in place of sodiumhydroxide show surprisingly higher selectivity for4,4′-dihydroxybiphenyl product in various organic solvent-water mixtures(compare Examples 11-14 with Examples 7-10). Examples wherein potassiumhydroxide was used in place of sodium hydroxide also show bothsurprisingly higher conversion of starting material and higherselectivity for 4,4′-dihydroxybiphenyl product in methanol-water solventmixtures (compare Examples 20-22 with Examples 16-18). Examples 4-6 showthat the increase in selectivity for 4,4′-dihydroxybiphenyl begins tolevel off at some concentration of potassium hydroxide above about 1equivalent. Examples wherein a methanol-water mixture was used showsurprisingly higher selectivity for 4,4′-dihydroxybiphenyl product thando similar Examples wherein water alone was employed as solvent, nomatter what base is employed, as seen in comparing Example 15 withExamples 16-18 and also in comparing Example 19 with Examples 20-22.

EXAMPLE 23

A reductive coupling reaction is performed under the same conditions asdescribed for Example 21 using the same reaction mixture componentsexcept that hydrogen gas is diluted with an inert gas such as argon ornitrogen such that the mole % of hydrogen present is in a range ofbetween about 40 mole % and about 99 mole %, based on total moles gaspresent and the partial pressure of hydrogen gas is 103 kPa. Theconversion of starting material and selectivity for4,4′-dihydroxybiphenyl product is higher than that obtained when thepartial pressure of hydrogen gas in the reaction mixture is 1723 kPa.

While the invention has been illustrated and described in typicalembodiments, it is not intended to be limited to the details shown,since various modifications and substitutions can be made withoutdeparting in any way from the spirit of the present invention. As such,further modifications and equivalents of the invention herein disclosedmay occur to persons skilled in the art using no more than routineexperimentation, and all such modifications and equivalents are believedto be within the spirit and scope of the invention as defined by thefollowing claims. All Patents cited herein are incorporated herein byreference.

What is claimed is:
 1. A method for preparing a bis(hydroxy-aromatic)compound which comprises the step of: contacting at least onehalo-substituted hydroxy-aromatic compound in a solvent mixturecomprising water and at least one organic solvent in the presence of atleast one base, at least one catalyst comprising palladium and hydrogengas at a pressure in a range of between atmospheric pressure and 350kilopascals.
 2. The method of claim 1 wherein the halo-substitutedhydroxy-aromatic compound is selected from the group consisting ofbromo-substituted hydroxy-aromatic compounds, chloro-substitutedhydroxy-aromatic compounds and mixtures thereof.
 3. The method of claim1 wherein the halo-substituted hydroxy-aromatic compound is additionallysubstituted with at least one substituent selected from the groupconsisting of alkyl, aryl, ether, alkyl ether, aryl ether, alkylalcohol, carboxylic acid, carboxylic ester, an additional hydroxysubstituent, an additional halogen substituent and mixtures thereof. 4.The method of claim 1 wherein the halo-substituted hydroxy-aromaticcompound is selected from the group consisting of 4-bromo-1-naphthol,4chloro-1-naphthol, 4-bromo-ortho-alkylphenol,4-chloro-ortho-alkylphenol, 4-bromo-ortho-cresol, 4-chloro-ortho-cresol,4-bromophenol and 4-chloro-phenol.
 5. The method of claim 1 wherein theorganic solvent is present in an amount in a range of between greaterthan 1 wt. % and less than 80 wt. % based on the weight of organicsolvent and water.
 6. The method of claim 1 wherein the organic solventis present in an amount in a range of between about 20 wt. % and about45 wt. % based on the weight of organic solvent and water.
 7. The methodof claim 1 wherein the organic solvent is substantially soluble inwater.
 8. The method of claim 1 wherein the organic solvent is selectedfrom the group consisting of alkyl alcohols, alkyl glycols and mixturesthereof.
 9. The method of claim 1 wherein the organic solvent isselected from the group consisting of methanol, ethanol, ethylene glycoland mixtures thereof.
 10. The method of claim 1 wherein thehalo-substituted hydroxy-aromatic compound is present in the solventmixture at a concentration of between about 5 wt. % and about 50 wt. %based on the weight of the entire reaction mixture.
 11. The method ofclaim 1 wherein the base is selected from the group consisting ofalkaline earth metal hydroxides, alkali metal hydroxides and mixturesthereof.
 12. The method of claim 11 wherein the base is selected fromthe group consisting of sodium hydroxide and potassium hydroxide. 13.The method of claim 1 wherein the base is present at a level of at leastone molar equivalent in relation to moles of the halo-substitutedhydroxy-aromatic compound.
 14. The method of claim 1 wherein the base ispresent in stoichiometric excess in relation to moles of thehalo-substituted hydroxy-aromatic compound.
 15. The method of claim 14wherein the base is present at a level in a range of between about 1.8molar equivalents and about 4 molar equivalents in relation to moles ofthe halo-substituted hydroxy-aromatic compound.
 16. The method of claim1 wherein the catalyst comprises palladium metal and an inert support.17. The method of claim 1 wherein the catalyst is present at a level ina range of between about 0.05 wt. % and about 4 wt. % based on theweight of the halo-substituted hydroxy-aromatic compound.
 18. The methodof claim 1 wherein hydrogen gas is at a pressure of less than about 200kilopascals.
 19. The method of claim 1 wherein hydrogen gas is at apressure of less than about 150 kilopascals.
 20. The method of claim 1wherein hydrogen gas is at a pressure of less than about 110kilopascals.
 21. A method for preparing a bis(hydroxy-aromatic) compoundwhich comprises the step of: contacting at least one halo-substitutedhydroxy-aromatic compound selected from the group consisting of4-bromo-ortho-alkylphenol, 4-chloro-ortho-alkylphenol,4-bromo-ortho-cresol, 4-chloro-ortho-cresol, 4-bromophenol and4-chloro-phenol, in a solvent mixture comprising water and 20-45 wt. %methanol based on the weight of methanol and water, in the presence ofpotassium hydroxide, at least one catalyst comprising palladium andhydrogen gas at a pressure in a range of between atmospheric pressureand 350 kilopascals.